COX-2 inhibitor nimesulide analogs are aromatase suppressors in breast cancer cells.

Abstract

Cyclooxygenase-2 (COX-2) inhibitor nimesulide derivatives compounds A and B decreased aromatase activity in breast cancer cells via a novel mechanism different to aromatase inhibitors (AIs), and were defined as "aromatase suppressors". Breast carcinoma cells (MCF-7aro and T47Daro) transfected with aromatase full gene were used to explore the mechanisms of the two compounds. They dose and time-dependently suppressed aromatase activity in MCF-7aro and T47Daro cells in the nanomole range. However, they neither directly inhibited aromatase, nor improved aromatase degradation even at much higher concentrations. They could also suppress androgen stimulated cell growth, but did not affect estrogen enhanced cell proliferation. These results suggest that compounds A and B selectively interfere with aromatase in breast cancer cells, but not estrogen receptor (ER) downstream to disrupt androgen mediated cell growth. Interestingly, compound B effectively inhibited LTED (long-term estrogen deprived MCF-7aro cell) cell growth, which is a model for AIs resistance, with an IC(50) of 4.68 ± 0.54 μM. The results indicate that compound B could potentially overcome AI resistance in breast cancer cell and could be used as a lead to design more potent derivatives.

• Authors: Bin Su, Xiaohan Cai, Yanyan Hong, Shiuan Chen
• Journal: The Journal of steroid biochemistry and molecular biology (J Steroid Biochem Mol Biol) Vol. 122 Issue 4 Pg. 232-8 (Oct 2010) ISSN: 1879-1220 [Electronic] England
• PMID: 20542113 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Published by Elsevier Ltd.

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Aromatase Inhibitors
• Cyclooxygenase 2 Inhibitors
• Estrogens
• Sulfonamides
• Testosterone
• Estradiol
• nimesulide

Topics

• Anti-Inflammatory Agents, Non-Steroidal (chemistry, pharmacology)
• Aromatase Inhibitors (chemistry, pharmacology)
• Breast Neoplasms (drug therapy)
• Carcinoma (drug therapy)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cyclooxygenase 2 Inhibitors (chemistry, pharmacology)
• Estradiol (metabolism)
• Estrogens (metabolism)
• Female
• Humans
• Sulfonamides (chemistry, pharmacology)
• Testosterone (metabolism)